Characterization of novel imidazole derivative, JM-8686, a potent inhibitor of allene oxide synthase

• Published in: FEBS letters Vol. 580; no. 24; pp. 5791 - 5796
• Main Authors: Oh, Keimei, Asami, Tadao, Matsui, Kenji, Howe, Gregg A., Murofushi, Noboru
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 16-10-2006
• Subjects: 13 (S) HPOT; 13 (S)-hydroperxy-9 (Z), 11 (E), 15 (Z)-octadecatrienoic acid; 8-[1-(2,4-dichloro-phenyl)-2-imidazol-1-yl-ethoxy]-octanoic acid heptyl ester; Allene oxide synthase; AOS; Arabidopsis - drug effects; Arabidopsis - enzymology; Arabidopsis thaliana allene oxide synthase; AtAOS; Caprylates - chemistry; Caprylates - pharmacology; DES; divinyl ether synthase; Enzyme Activation - drug effects; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; fatty acid hydroperoxide lyase; HPL; Imidazoles - chemistry; Imidazoles - pharmacology; Inhibitor; Intramolecular Oxidoreductases - antagonists & inhibitors; Intramolecular Oxidoreductases - metabolism; JAs; Jasmonates; jasmonic acid; Jasmonic acid biosynthesis; JM-8686; Kinetics; LeHPL; Lycopersicon esculentum fatty acid hydroperoxide lyase; Molecular Structure; Protein Binding; JM-8686; DES; Jasmonic acid biosynthesis; AOS; HPL; LeHPL; 13 ( S) HPOT; JA; Inhibitor; AtAOS; JAs; Allene oxide synthase
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2006.09.044

The inhibitory properties of a first synthetic jasmonic acid biosynthesis inhibitor, JM-8686, were investigated. Steady-state kinetic analysis indicates that the compound is a competitive inhibitor of allene oxide synthase (AOS) with a
K
i value of approximate 0.62
±
0.15
μM. Dialysis experiment indicates that AOS inactivation by JM-8686 is reversible. The optical difference spectroscopy analysis of JM-8686 and AOS interaction indicates that JM-8686 induced type II binding spectra with a
K
d value of approximate 1.6
±
0.2
μM, suggesting that JM-8686 binds to the prosthetic heme iron of AOS. Comparison of the inhibitory potency of the compound against HPL (CYP74B) from tomato revealed that JM-8686 was a highly selective inhibitor for AOS.